Infectious diseases caused by human acquired immunodeficiency virus (HIV), which is a type of retrovirus, have recently become a serious social problem. A compound of 3'-deoxy-3'-azidothymidine is known as a nucleoside compound used in the clinical treatment for diseases caused by HIV-infection. However, this compound has side-effects since it also exhibits considerable strong toxicity in the host cells.
Although some 2', 3'-dideoxyribonucleosides are known as nucleoside compounds exhibiting an anti-viral activity, it is still necessary to develop a substance possessing a higher activity and lower toxicity to the host cell (Hiroaki Mitsuya, Bodily Defense, Vol. 4, pp.213-223 (1987)).
On the other hand, various acyclonucleoside compounds have been synthesized since Acyclovir (acycloguanosine) was developed as an antiviral substance effective against herpes virus (C. K. Chu and S. J. Culter, J. Heterocyclic Chem., 23, p.289 (1986)). However, no acyclonucleoside compound having a sufficient activity especially against retroviruses has yet been discovered.
We have focussed our attention on 6-substituted acyclopyrimidine nucleoside compounds and have synthesized various novel 6-substituted acyclopyrimidine nucleoside derivatives and screened those compounds to detect effective antiviral agents, especially to the retrovirus, in order to provide antiviral agents exhibiting an effective activity particularly against retroviruses.
Some 6-substituted acyclopyrimidine nucleoside compounds such as 6-fluoro substituted derivatives, 6-alkylamino substituted derivatives (DD-A-232492) and 6-methyl substituted derivatives (C. A. 107, 129717w (1987)) are known; however, the antiviral activity of these compounds has not been described.
As a result of our researches for compounds exhibiting an effective antiviral activity, particularly anti-retroviral activity, we found that specific 6-substituted pyrimidine nucleoside compounds according to the invention satisfy the above demand to achieve the present invention.